Dorsal raphe GABA-ergic neurons regulate the susceptibility to social transfer of pain in mice.

IF 6.9 1区 医学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Acta Pharmacologica Sinica Pub Date : 2025-07-01 Epub Date: 2025-02-26 DOI:10.1038/s41401-025-01494-x
Lin Ai, Yi Han, Ting Ge, Sha Sha, Xiao-Jing Zhai, Ran Ji, Yu Zhou, Dan-Dan Chen, An Xie, Wen-Xin Zhang, Zhou Wu, Mo-Ruo Zhang, Jun-Xia Yang, An-Kang Hu, Jun-Li Cao, Ling-Zhen Song, Hong-Xing Zhang
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引用次数: 0

Abstract

Some individuals are more susceptible to developing or suffering from pain states than others. However, the brain mechanisms underlying the susceptibility to pain responses are unknown. In this study, we defined pain susceptibility by recapitulating inter-individual differences in pain responses in mice exposed to a paradigm of socially transferred allodynia (STA), and with a combination of chemogenetic, molecular, pharmacological and electrophysiological approaches, we identified GABA-ergic neurons in the dorsal raphe nucleus (DRN) as a cellular target for the development and maintenance of STA susceptibility. We showed that DRN GABA-ergic neurons were selectively activated in STA-susceptible mice when compared with the unsusceptible (resilient) or control mice. Chemogenetic activation of DRN GABA-ergic neurons promoted STA susceptibility; whereas inhibiting these neurons prevented the development of STA susceptibility and reversed established STA. In in vitro slice electrophysiological analysis, we demonstrated that melanocortin 4 receptor (MC4R) enriched in DRN GABA-ergic neurons was a molecular target for regulating pain susceptibility, possibly by affecting DRN GABA-ergic neuronal activity. These results establish the DRN GABA-ergic neurons as an essential target for controlling pain susceptibility, thus providing important information for developing conceptually innovative and more accurate analgesic strategies.

中缝背gaba能神经元调节小鼠对疼痛社会转移的易感性。
有些人比其他人更容易发展或遭受疼痛状态。然而,对疼痛反应易感性的大脑机制尚不清楚。在这项研究中,我们通过概括暴露于社会转移性异常性疼痛(STA)范式的小鼠疼痛反应的个体间差异来定义疼痛易感性,并结合化学发生,分子,药理学和电生理学方法,我们确定中缝背核(DRN)中的gaba -能神经元是STA易感性发展和维持的细胞靶点。我们发现,与不敏感(弹性)或对照小鼠相比,sta易感小鼠的DRN gaba能神经元被选择性激活。DRN - gaba -能神经元的化学激活促进STA易感性;而抑制这些神经元可阻止STA易感性的发展并逆转已建立的STA。通过体外电生理片分析,我们发现DRN gaba -能神经元中富集的黑素皮质素4受体(melanocortin 4 receptor, MC4R)是调节疼痛敏感性的分子靶点,可能通过影响DRN gaba -能神经元的活性来实现。这些结果证实DRN gaba能神经元是控制疼痛易感性的重要靶点,从而为开发概念创新和更准确的镇痛策略提供了重要信息。
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来源期刊
Acta Pharmacologica Sinica
Acta Pharmacologica Sinica 医学-化学综合
CiteScore
15.10
自引率
2.40%
发文量
4365
审稿时长
2 months
期刊介绍: APS (Acta Pharmacologica Sinica) welcomes submissions from diverse areas of pharmacology and the life sciences. While we encourage contributions across a broad spectrum, topics of particular interest include, but are not limited to: anticancer pharmacology, cardiovascular and pulmonary pharmacology, clinical pharmacology, drug discovery, gastrointestinal and hepatic pharmacology, genitourinary, renal, and endocrine pharmacology, immunopharmacology and inflammation, molecular and cellular pharmacology, neuropharmacology, pharmaceutics, and pharmacokinetics. Join us in sharing your research and insights in pharmacology and the life sciences.
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